Experiment
163 microsatellite markers at an average spacing of 10 cM were typed in 95 (C57BL/6J x DBA/2J)F2 animals to detect loci associated with resistance to infection by Mycobacterium tuberculosis. Animals were infected intravenously with 1 x 105 M.tuberculosis H37Rv and measured for survival time. Parental inbred strain DBA/2J is highly susceptible to tuberculosis (105 day mean survival time) whereas C57BL/6J is resistant (240 day mean survival time). Tuberculosis resistance loci were detected on mouse chromosome 1 from 67 cM - 95.8 cM (Tbrs1, LOD = 4.8 at D1Mit265, D1Mit396, and D1Mit425), mouse Chromosome 3 from 29.5 cM - 39.7 cM (Tbrs2, LOD = 3.93 at D3Mit241 and D3Mit51), and mouse Chromosome 7 from 0.5 cM - 37 cM (Tbrs3, LOD = 4.66 at D7Mit117, D7Mit270, and D7Mit228). C57BL/6J-derived alleles confer recessively inherited resistance at Tbrs1, dominantly inherited resistance at Tbrs2, and additively inherited resistance at Tbrs3. Pairwise analyses detected strong additive interaction between Tbrs1 and Tbrs3. Possible candidate genes in the region of Tbrs1 are chemokine (C-X-C) receptor 4 (Cxcr4), interleukin 10 (1l10), neutrophil cytosolic factor 2 (Ncf2), tumor necrosis factor (ligand) superfamily, member 6 (Fasl, formerly Tbfsf6L), and a cluster of selectins (Sele, Sell, and Selp). Tbrs1 maps near Tir3, a QTL associated with susceptibility to trypanosomiasis in a BALB/cJ x C57BL/6J cross. Possible candidate genes for Tbrs2 are interleukin 2 (Il2), interleukin 12a (Il12a), and interleukin 6 receptor, alpha(Il6ra). Tbrs3 does not appear to map near any obvious candidate genes.
Analysis Tools